The proposed Career Development Award will help Dr. Susan McCami gain independence in a career focused on the nutritional epidemiology of chronic disease, integrating her background in nutritional sciences and epidemiology, and gaining new expertise in molecular epidemiology. Her immediate goals as outlined below include an investigation of tho relationship between food components with hormonal activities (phytoestrogens) and breast cancer risk using retrospective and experimental designs and to collaborate with ongoing research in the Department of Social and Preventive Medicine (SPM). SPM has a long history of research in diet and cancer and is ideally suited for this research. In addition, she will receive training and insight into the integration of laboratory methods into epidemiology and the inclusion of genetic susceptibility in epidemiologic studies, and further training in onclogy, molecular epidemiology, and endocrinology. Proposed here are two studies examining the role of dietary phytoestrogens in the etiology of pre- and postmenopausal breast cancer. The first utilizes data from a large case-control study for which data collection is currently ongoing (ending Spring 2001). Analyses will examine rite relationship between dietary intakes of lignans (major phytoestrogen source) on breast cancer risk. Data from the controls will be utilized to examine the relationship between dietary lignan intake and other dietary, non-dietary, and biomarkers of nutrition and chronic disease risk factors. Finally, we will examine genetic susceptibility as a modifying factor on these relationships by estimating risk stratified by polymorphisms of genes related to estrogen metabolism, CYP 17 and COMT. The second study involves collection of new data investigating the effect of dietary lignan supplementation on serum estrogen and phytoestrogen levels, and the impact of CYP17 and COMT polymorphisms on this relationship. Subjects in the study will consume flaxseed supplements for seven days and differences between baseline and postsupplementation serum estrogen and phytoestrogen levels assessed. These investigations, combining retrospective and experimental designs, as well as genetic analyses, will help to elucidate the role of dietary phytoestrogen intake in the etiology of a hormone- sensitive cancer.